In many "in vitro" studies, drug metabolites have been shown to alter the metabolism of the parent compound. These results observed in the "in vitro" studies should be extended and corroborated in the whole animal. Whether this occurs depends on the pharmacokinetic profile of the metabolite. This would include such parameters as the volume of distribution, the half-life and the accumulation of the metabolite after chronic administration. After establishing the pharmacokinetic parameters of the disposition of diazepam and its metabolites in the rabbit by a single intravenous bolus of the drug, we will infuse each of these drugs until a number of steady state levels are achieved. When the blood levels are constant, usually requiring a time of approximately five times the elimination half-life of the compund, an intravenous bolus of diazepam or its metabolite will be administered and its pharmacokinetic profile determined. Whole blood levels and urinary elimination of diazepam, desmethyldiazepam and oxazepam will be monitored using electron capture gas-liquid chromatography. The results of the proposed study would allow the determination of 1) the time course of metabolite accumulation in relation to steady state blood levels, 2) the effects of metabolite accumulation on the pharmacokinetic disposition of diazepam and desmethyldzepam and 3) an insight into the general nature of metabolite accumulation and drug efficacy.